Spatial distribution of residential environment, genetic susceptibility, and psoriasis: A prospective cohort study

Background Genetic and environmental factors contribute to psoriasis, but the impact of residential environments on this condition remains uncertain. We aimed to investigate the association of residential environments with psoriasis risk and explore its interaction with genes. Methods We retrieved data on the spatial distribution of residential environments at 300 and 1000 m buffer zones from the UK Biobank, including the proportions of natural environments, domestic gardens, green spaces, and blue spaces within these zones. We then used Cox hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between residential environments and psoriasis risk. Lastly, we constructed polygenic risk scores to determine genetic susceptibility and further analyse the interaction with residential environments. Results Overall, 3755 incident cases of psoriasis were documented during a median follow-up of 12.45 years. Compared with the lowest exposure quantile (Q1), Q4 exposure to natural environments (1000 m buffer: HR = 1.16, 95% CI = 1.05–1.29; 300 m buffer: HR = 1.12, 95% CI = 1.02–1.24) and green spaces (1000 m buffer: HR = 1.16, 95% CI = 1.04–1.28; 300m buffer: HR = 1.10, 95% CI = 1.00–1.21) increased the risk of psoriasis, while Q4 exposure to domestic gardens (1000 m buffer: HR = 0.85, 95% CI = 0.77–0.93; 300m buffer: HR = 0.91, 95% CI = 0.83–1.00) and Q3 exposure to blue spaces (1000 m buffer: HR = 0.89, 95% CI = 0.81–0.98) were negatively associated with psoriasis risk. Among participants with a high genetic risk, those exposed to high levels of natural environments (1000 m buffer: HR = 1.49, 95% CI = 1.15–1.93; 300 m buffer: HR = 1.39, 95% CI = 1.10–1.77) and green spaces (300 m buffer: HR = 1.30, 95% CI = 1.04–1.64) had a higher risk of psoriasis, while those exposed to blue spaces (1000 m buffer: HR = 0.78, 95% CI = 0.63–0.98) had a lower risk of psoriasis. We also observed joint effects of genetic risk and residential environments and an antagonistic additive interaction between blue spaces and genetic risk (P = 0.011). Conclusions We observed that residing in natural environments and green areas increased the risk of psoriasis in our sample, while proximity to blue spaces and domestic gardens was associated to reduced risks. The association of residential environments with psoriasis risk was modified by genetic susceptibility.


Supplementary materials
Figures: Figure S1.The flowchart of participant selection from UK Biobank. Figure S2.Directed acyclic graph.Figure S3.Pearson's correlation matrix among residential natural environment, domestic garden, green space, and blue space.Figure S4.The dose-response relationship of residential natural environment, domestic garden, green space, and blue space with incident psoriasis assessed by restricted cubic spline regression.
Figure S5.Stratified analyses of the associations of residential natural environment, domestic garden, green space, and blue space with incident psoriasis.Figure S6.Hazard ratio of psoriasis risk based on residential natural environment, domestic garden, green space and blue space stratified by Standard PRS. Figure S7.Joint effects of residential natural environment, domestic garden, green space and blue space with Standard PRS on the risk of psoriasis risk.

Tables:
Table S1.Distribution of residential natural environment, domestic garden, green space, and blue space at baseline.Table S2.PAR% of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis.Table S3.Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after further adjusting for HbA1c, triglyceride and systolic blood pressure.Table S4.Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after further adjusting for lymphocyte percentage, white blood cell count, and C-reactive protein.Table S5.Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after further adjusting for cancer, diabetes, and cardiovascular disease.Table S6.Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after restricting participants living at the same address >3 years.Table S7.Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis with the imputation of covariates.Table S8.Additive and multiplicative interactions of residential natural environment and domestic garden, and green space and blue space on the risk of incident psoriasis.Table S9.Summary results of SNPs used for PRS in the study.Table S10.Hazard ratio of psoriasis risk based on PRS.Table S11.Additive and multiplicative interactions of residential natural environment, domestic garden, green space, and blue space with PRS on the risk of incident psoriasis.Table S12.Hazard ratio of psoriasis risk based on Standard PRS.Table S13.Additive and multiplicative interactions of residential natural environment, domestic garden, green space, and blue space with Standard PRS on the risk of incident psoriasis.
Table S3.Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after further adjusting for HbA1c, triglyceride and systolic blood pressure.Abbreviations: CI, confidence interval; Q, quantile.Abbreviations: PRS, polygenic risk score; RERI, relative excess risk due to interaction; AP, attributable proportion due to interaction; CI, confidence interval.

Figure S1 .
Figure S1.The flowchart of participant selection from UK Biobank.

Figure S2 .
Figure S2.The directed acyclic graphs for the effect of spatial distribution of residential environment on psoriasis.

Figure S3 .
Figure S3.Pearson's correlation matrix among residential natural environment, domestic garden, green space, and blue space.

Figure S4 .
Figure S4.The dose-response relationship of residential natural environment, domestic garden, green space, and blue space with incident psoriasis assessed by restricted cubic spline regression.Models were adjusted for age, sex, body mass index, ethnicity, Townsend deprivation index, smoking status, alcohol intake, physical activity, and living score.

Figure S5 .
Figure S5.Stratified analyses of the associations of residential natural environment, domestic garden, green space, and blue space with incident psoriasis.Models were adjusted for age, sex, body mass index, ethnicity, Townsend deprivation index, smoking status, alcohol intake, physical activity, and living score.Abbreviations: Q, quantile.

Figure S6 .
Figure S6.Hazard ratio of psoriasis risk based on residential natural environment, domestic garden, green space and blue space stratified by Standard PRS.Models were adjusted for age, sex, body mass index, ethnicity, smoking status, alcohol intake, Townsend deprivation index, physical activity, living score, genotyping batch, and genetic principal components.

Figure S7 .
Figure S7.Joint effects of residential natural environment, domestic garden, green space and blue space with PRS on the risk of psoriasis risk.Models were adjusted for age, sex, body mass index, ethnicity, smoking status, alcohol intake, Townsend deprivation index, physical activity, living score, genotyping batch, and genetic principal components.Abbreviations: RA, rheumatoid arthritis; PRS, polygenic risk score, Q, quantile.

Table S1 .
Distribution of residential natural environment, domestic garden, green space, and blue space at baseline.

Table S2 .
PAR% of residential natural environment, domestic garden, green space, and blue space with incident

Table S4 .
Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after further adjusting for lymphocyte percentage, white blood cell count, and C-reactive protein.

Table S5 .
Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after further adjusting for cancer, diabetes, and cardiovascular disease.
Models were adjusted for age, sex, body mass index, ethnicity, Townsend deprivation index, smoking status, alcohol intake, physical activity, living score, cancer, diabetes, and cardiovascular disease.Abbreviations: CI, confidence interval; Q, quantile.

Table S6 .
Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis after restricting participants living at the same address >3 years.

Table S7 .
Associations of residential natural environment, domestic garden, green space, and blue space with the risk of incident psoriasis with the imputation of covariates.

Table S8 .
Additive and multiplicative interactions of residential natural environment and domestic garden, green space and blue space on the risk of incident psoriasis.

Table S9 .
Summary results of SNPs used for PRS in the study.

Table S10 .
Hazard ratio of psoriasis risk based on PRS.

Table S11 .
Additive and multiplicative interactions of residential natural environment, domestic garden, green space, and blue space with PRS on the risk of incident psoriasis.
Abbreviations: PRS, polygenic risk score; RERI, relative excess risk due to interaction; AP, attributable proportion due to interaction; CI, confidence interval.

Table S12 .
Hazard ratio of psoriasis risk based on Standard PRS.

Table S13 .
Additive and multiplicative interactions of residential natural environment, domestic garden, green space, and blue space with Standard PRS on the risk of incident psoriasis.Models were adjusted for age, sex, body mass index, ethnicity, smoking status, alcohol intake, Townsend deprivation index, physical activity, living score, genotyping batch, and genetic principal components.